Nano-catalytic behavior of CeO2 nanoparticles in dye adsorption: Synthesis through bio-combustion and assessment of UV-light-driven photo-adsorption of indigo carmine dye.

This study explores the adsorption of indigo carmine dye using bio-combusted cerium oxide nanoparticles (CeO2 NPs). CeO2 NPs were synthesized using a bio-combustion method, and then subjected to structural, morphological, and optical characterization for thorough investigation. Structural investigation was carried out using X-ray diffraction (XRD), which revealed a cubic structure with evaluated average crystallite size of 11.55 nm. Later, the same was verified by employing W-H plot (13.57 nm). UV-Vis spectroscopy revealed an effective band gap of 3 eV suited for photocatalytic applications. The metal-oxygen phonon band at 986.32 cm-1 and 871.96 cm-1 is confirmed using Infrared Spectroscopy (FTIR). The morphological analysis was done using Transmission and Scanning Electron Microscopy (TEM and SEM), which revealed well-dispersed, aggregated structure enclosing spherical nanoparticles with an average size of ∼14 nm. The early precursors were validated using EDAX analysis and SEM. Optical characteristics were investigated using photoluminescence (PL), which revealed a large charge transfer band between 360 nm and 435 nm. The dye removal efficiency of CeO2 NPs was evaluated against Indigo Carmine dye using UV light. The results showed that the significantly adsorption, with more than 70 % removed after 150 min. Kinetic experiments revealed that the depreciation occurred via a pseudo-first-order reaction process. Furthermore, the impacts of certain factors such as dye dosage, pH, reusability, and scavenger on adsorption rate were explored and shown to be effective values for the adsorption process. This study emphasizes the potential of CeO2 NPs as excellent photocatalysts for environmental remediation, especially in dye removal applications.

A review on vulnerable atmospheric aerosol nanoparticles: Sources, impact on the health, ecosystem and management strategies.

The Earth's atmosphere contains ultrafine particles known as aerosols, which can be either liquid or solid particles suspended in gas. These aerosols originate from both natural sources and human activities, termed primary and secondary sources respectively. They have significant impacts on the environment, particularly when they transform into ultrafine particles or aerosol nanoparticles, due to their extremely fine atomic structure. With this context in mind, this review aims to elucidate the fundamentals of atmospheric-derived aerosol nanoparticles, covering their various sources, impacts, and methods for control and management. Natural sources such as marine, volcanic, dust, and bioaerosols are discussed, along with anthropogenic sources like the combustion of fossil fuels, biomass, and industrial waste. Aerosol nanoparticles can have several detrimental effects on ecosystems, prompting the exploration and analysis of eco-friendly, sustainable technologies for their removal or mitigation.Despite the adverse effects highlighted in the review, attention is also given to the generation of aerosol-derived atmospheric nanoparticles from biomass sources. This finding provides valuable scientific evidence and background for researchers in fields such as epidemiology, aerobiology, and toxicology, particularly concerning atmospheric nanoparticles.

Transient stabilization of human cardiovascular progenitor cells from hPSCs in vitro reflects stage-specific heart development in vivo.

AIM: Understanding the molecular identity of human pluripotent stem cell (hPSC)-derived cardiac progenitors and mechanisms controlling their proliferation and differentiation, is valuable for developmental biology and regenerative medicine. METHODS AND RESULTS: Here we show that chemical modulation of Histone Acetyl Transferases (HATs; by IQ-1) and WNT (by CHIR99021), synergistically enable the transient and reversible block of directed cardiac differentiation progression on hPSCs. The resulting stabilized cardiovascular progenitors (SCPs) are characterized by ISL1pos/KI-67pos/NKX2-5neg expression. In the presence of the chemical inhibitors, SCPs maintain a proliferation quiescent state. Upon small molecules removal SCPs resume proliferation and concomitant NKX2-5 upregulation triggers cell-autonomous differentiation into cardiomyocytes. Directed differentiation of SCPs into the endothelial and smooth muscle lineages confirms their full developmental potential typical of bona fide cardiovascular progenitors. Single-cell RNAseq-based transcriptional profiling of our in vitro generated human SCPs notably reflects the dynamic cellular composition of E8.25-E9.25 posterior second heart field (pSHF) of mouse hearts, hallmarked by NR2F2 expression. Investigating molecular mechanisms of SCP stabilization, we found that the cell-autonomously regulated Retinoic Acid (RA) and BMP signaling is governing SCPs transition from quiescence towards proliferation and cell-autonomous differentiation, reminiscent of a niche-like behavior. CONCLUSION: The chemically defined and reversible nature our stabilization approach provides an unprecedented opportunity to dissect mechanisms of cardiovascular progenitors' specification and reveal their cellular and molecular properties.

Developmental Formulation Principles of Food Preservatives by Nanoencapsulation-Fundamentals, Application, and Challenges.

The role of food additives is to preserve food by extending shelf life and limiting harmful microorganism proliferation. They prevent spoilage by enhancing the taste and safety of food by utilizing beneficial microorganisms and their antimicrobial metabolites. Current advances in food preservation and processing utilize green technology principles for green preservative formulation, enhancing nutrition and supplying essential micronutrients safely, while also improving quality, packaging, and food safety. Encapsulation is gaining attention for its potential to protect delicate materials from oxidative degradation and extend their shelf life, thereby ensuring optimal nutrient uptake. Nanoencapsulation of bioactive compounds has significantly improved the food, pharmaceutical, agriculture, and nutraceutical industries by protecting antioxidants, vitamins, minerals, and essential fatty acids by controlling release and ensuring delivery to specific sites in the human body. This emerging area is crucial for future industrial production, improving the sensory properties of foods like color, taste, and texture. Research on encapsulated bioactive compounds like bacteriocins, LAB, natamycin, polylysine, and bacteriophage is crucial for their potential antioxidant and antimicrobial activities in food applications and the food industry. This paper reviews nanomaterials used as food antimicrobial carriers, including nanoemulsions, nanoliposomes, nanoparticles, and nanofibers, to protect natural food antimicrobials from degradation and improve antimicrobial activity. This review discusses nanoencapsulation techniques for biopreservative agents like nisin, poly lysine, and natamycin, focusing on biologically-derived polymeric nanofibers, nanocarriers, nanoliposomes, and polymer-stabilized metallic nanoparticles. Nanomaterials, in general, improve the dispersibility, stability, and availability of bioactive substances, and this study discusses the controlled release of nanoencapsulated biopreservative agents.

Histopathological significance of necrosis in oral lesions: A review.

Necrosis is a localized area of tissue death followed by degradation of tissue by hydrolytic enzymes released from the dead cells, resulting in swelling of organelles, rupture of the plasma membrane, eventual cell lysis, and leakage of intracellular contents into the surrounding tissue. It is always accompanied by an inflammatory reaction. Necrosis is caused by various factors such as hypoxia, physical factors, chemical agents, immunological agents, and microbial agents. Still now, there is no literature review regarding the necrotic lesions of the oral cavity. In this paper, the oral lesions associated with necrosis are categorized under the headings such as odontogenic cysts, odontogenic tumors, salivary gland pathology, and epithelial malignancies. In addition, the histopathological significance of necrosis in oral lesions has been discussed. By suggesting that spotting necrosis in the histopathology aids in determining the diagnosis, tumor behavior, and prognosis of oral lesions.

Microplastics everywhere: A review on existing methods of extraction.

Microplastics (MPs) are a ubiquitous pollutant. They take the form of fibers, fragments, microbeads, pellets, and foams, slowly choking up waterways, the atmosphere, and, eventually, the food chain. As the need for analysis and removal of these polymers takes on a role of utmost importance, it becomes imperative to know the methods by which these micro-pollutants can be extracted from the environmental matrices in which they appear. This review aims to compile the various methods of MP extraction available in literature. With general methods like density separation and the oil extraction protocol listed alongside research on process-based separation using ultrasound and fluid dynamics, there may be a way to create a standardized protocol for the mass extraction of MPs from any environmental matrix.

Stabilizing Polar Domains in MAPbBr3 via the Hydrostatic Pressure-Induced Liquid Crystal-like Transition.

Pressure-induced phases of MAPbBr3 were investigated at room temperature in the range of 0-2.8 GPa by ab initio molecular dynamics. Two structural transitions at 0.7 GPa (cubic → cubic) and 1.1 GPa (cubic → tetragonal) involved both the inorganic host (lead bromide) and the organic guest (MA). MA dipoles behave like a liquid crystal undergoing isotropic → isotropic and isotropic → oblate nematic transitions as pressure confines their orientational fluctuations to a crystal plane. Beyond 1.1 GPa, the MA ions lie alternately along two orthogonal directions in the plane forming stacks perpendicular to it. However, the molecular dipoles are statically disordered, leading to stable polar and antipolar MA domains in each stack. H-Bond interactions, which primarily mediate host-guest coupling, facilitate the static disordering of MA dipoles. Interestingly, high pressures suppress CH3 torsional motion, emphasizing the role of C-H···Br bonds in the transitions.

Role of Reflux Symptom Index and Reflux Finding Score in Diagnosing Laryngopharyngeal Reflux: A Prospective Study.

Laryngopharyngeal Reflux Disease (LPRD) is caused due to reflux of gastric content into the larynx and pharynx. The present study was done to assess the role of Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) in the treatment outcomes in symptomatic patients with LPRD. This is a prospective analytical study conducted on 200 patients for a period of 2 years, from January 2020 to February 2022. Patients suspected with LPR were evaluated using RSI and RFS, and both pre and post treatment scores were compared to assess the change in scores of RSI and RFS following 8 weeks of treatment with PPI (Proton pump inhibitor). The patients experienced a greater incidence of moderate symptoms in RSI. Wilcoxon signed-rank test showed significant difference between pre and post treatment scores with respect to reflux symptoms and reflux findings (p < 0.05). Implementation of RSI and RFS scoring system helped for early diagnosis of LPR, and a significant difference was seen between pre and post treatment scores in both RSI and RFS.

Heteroleptic Cu(I) bis-diimine complexes as sensitizers in dye-sensitized solar cells (DSSCs): on some factors affecting intramolecular charge transfer.

A set of eight heteroleptic bis-diimine copper dye complexes with two different ancillary ligands (functionalised 2,9-dimethyl-1,10-phenanthroline (dmp) and functionalised 6,6'-diphenyl-2,2'-bipyridine (dpbpy)) are investigated for their potential use as sensitizers in dye-sensitized solar cells (DSSCs), using first principles density functional theory (DFT) and time dependent DFT (TDDFT). A detailed analysis of the structural properties, projected density of electronic states and Kohn-Sham energy levels, and optical absorption spectra in the UV-visible region reveals that substituting the thiophene group in the ancillary ligand, and enhancing conjugation in the anchoring ligand, lead to increase in the light harvesting efficiency (LHE). However, a natural transition orbital (NTO) analysis, shows that the nature of charge transfer depends mainly on the nature of the parent ancillary group and is not significantly affected by the structural modifications. Importantly, the lower energy excitations lead to favourable mixed metal to ligand charge transfer (MLCT) and ligand to ligand charge transfer (LLCT), as well as good electron injection. The best charge transfer directionality is found in the dmp-based dyes, particularly thiophene substituted dyes, thus making these the more effective sensitizers in DSSCs.

"Fizz Sign" in Acute Sinusitis-A CT Scan Finding.

To study the Computerized Tomography (CT) Paranasal Sinus findings in patients with acute bacterial sinusitis and the clinical symptom associated with it. 120 patients were examined over 2 years with coronal CT images of paranasal sinus with clinical symptoms of acute sinusitis of 2 weeks duration from the onset. Patients with symptoms of more than 2 weeks and patients with chronic sinusitis, immunocompromised status were excluded. Air mixed with fluid is seen like a Fizz of cola drink within the maxillary, frontal or sphenoid sinus, mucosal thickening of more than 5 mm, fluid level and presence of opacifications were used as evidence of acute sinusitis. 28 patients (23.3%) had Fizz sign (Air mixed with fluid seen as bubbles) coronal CT images of the paranasal sinus. The study demonstrated great variation in the CT paranasal findings amongst patients with suspected acute sinusitis. More than one sinus subsite was affected amongst patients in whom acute sinusitis was confirmed by CT Paranasal sinus imaging. We hereby highlight a new sign of air mixed with fluid which the senior author had named as Fizz Sign because of its resemblance to the fizz of dark cola drink.

Expression sites of immunohistochemistry markers in oral diseases - A scoping review.

Introduction: Immunohistochemistry (IHC) has not always been an easy field for the research beginners like postgraduates, research fellows and scientists. Meaningful interpretation of IHC positivity needs expertise. This could be made easier for beginners by developing a conceptual framework of markers. The literature review revealed a lack of qualitative evidence on the hitherto IHC studies on oral diseases about the overall expression of IHC markers and its comparison with pathology and normal tissues. Aim: This scoping review aimed to examine the literature and classify the various immunohistochemistry markers of oral diseases based on the tissue, cell and site of expression. Materials and Methods: The review was in accordance with Preferred Reporting Items for scoping reviews (PRISMA -ScR). Electronic databases such as PubMed and Cochrane were searched for relevant articles till 2021. Results: We included 43 articles. We found five different possibilities of the site of expression of a marker in a cell. They are the nucleus, cytoplasm, cell membrane, extracellular matrix or any of the above combinations. Based on the tissue of expression, we also mapped the markers expressed in oral diseases to their tissue of origin as ectoderm, endoderm, mesoderm and markers with multiple tissues of expression. Based on our results, we derived two classifications that give an overview of the expression of IHC markers in oral diseases. Conclusion: This scoping review derived new insight into the classification of IHC markers based on cell lineage, tissue and site of expression. This would enable a beginner to better understand a marker with its application and the interpretation of the staining in research. This could also serve as a beginner's guide for any researcher to thrive and explore the IHC world.

Pressure induced topochemical polymerization of solid acrylamide facilitated by anisotropic response of the hydrogen bond network.

The pressure induced polymerization of molecular solids is an appealing route to obtain pure, crystalline polymers without the need for radical initiators. Here, we report a detailed density functional theory (DFT) study of the structural and chemical changes that occur in defect free solid acrylamide, a hydrogen bonded crystal, when it is subjected to hydrostatic pressures. While our calculations are able to reproduce experimentally measured pressure dependent spectroscopic features in the 0-20 GPa range, our atomistic analysis predicts polymerization in acrylamide at a pressure of ∼23 GPa at 0 K albeit through large enthalpy barriers. Interestingly, we find that the two-dimensional hydrogen bond network in acrylamide templates topochemical polymerization by aligning the atoms through an anisotropic response at low pressures. This results not only in conventional C-C, but also unusual C-O polymeric linkages, as well as a new hydrogen bonded framework, with both N-HO and C-HO bonds. Using a simple model for thermal effects, we also show that at 300 K, higher pressures significantly accelerate the transformation into polymers by lowering the barrier. Thus, application of pressure offers an alternative route for topochemical polymerization when higher temperatures are undesirable.

Preclinical evidence for the therapeutic value of TBX5 normalization in arrhythmia control.

AIMS: Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mechanisms, we aimed to reveal the ventricular TBX5-dependent transcriptional network and further test the therapeutic potential of TBX5 level normalization in mice with documented arrhythmias. METHODS AND RESULTS: We used a mouse model of TBX5 conditional deletion in ventricular cardiomyocytes. Ventricular (v) TBX5 loss in mice resulted in mild cardiac dysfunction and arrhythmias and was associated with a high mortality rate (60%) due to SCD. Upon angiotensin stimulation, vTbx5KO mice showed exacerbated cardiac remodelling and dysfunction suggesting a cardioprotective role of TBX5. RNA-sequencing of a ventricular-specific TBX5KO mouse and TBX5 chromatin immunoprecipitation was used to dissect TBX5 transcriptional network in cardiac ventricular tissue. Overall, we identified 47 transcripts expressed under the control of TBX5, which may have contributed to the fatal arrhythmias in vTbx5KO mice. These included transcripts encoding for proteins implicated in cardiac conduction and contraction (Gja1, Kcnj5, Kcng2, Cacna1g, Chrm2), in cytoskeleton organization (Fstl4, Pdlim4, Emilin2, Cmya5), and cardiac protection upon stress (Fhl2, Gpr22, Fgf16). Interestingly, after TBX5 loss and arrhythmia development in vTbx5KO mice, TBX5 protein-level normalization by systemic adeno-associated-virus (AAV) 9 application, re-established TBX5-dependent transcriptome. Consequently, cardiac dysfunction was ameliorated and the propensity of arrhythmia occurrence was reduced. CONCLUSIONS: This study uncovers a novel cardioprotective role of TBX5 in the adult heart and provides preclinical evidence for the therapeutic value of TBX5 protein normalization in the control of arrhythmia.

Dysferlin links excitation-contraction coupling to structure and maintenance of the cardiac transverse-axial tubule system.

AIMS: The multi-C2 domain protein dysferlin localizes to the T-Tubule system of skeletal and heart muscles. In skeletal muscle, dysferlin is known to play a role in membrane repair and in T-tubule biogenesis and maintenance. Dysferlin deficiency manifests as muscular dystrophy of proximal and distal muscles. Cardiomyopathies have been also reported, and some dysferlinopathy mouse models develop cardiac dysfunction under stress. Generally, the role and functional relevance of dysferlin in the heart is not clear. The aim of this study was to analyse the effect of dysferlin deficiency on the transverse-axial tubule system (TATS) structure and on Ca2+ homeostasis in the heart. METHODS AND RESULTS: We studied dysferlin localization in rat and mouse cardiomyocytes by immunofluorescence microscopy. In dysferlin-deficient ventricular mouse cardiomyocytes, we analysed the TATS by live staining and assessed Ca2+ handling by patch-clamp experiments and measurement of Ca2+ transients and Ca2+ sparks. We found increasing co-localization of dysferlin with the L-type Ca2+-channel during TATS development and show that dysferlin deficiency leads to pathological loss of transversal and increase in longitudinal elements (axialization). We detected reduced L-type Ca2+-current (ICa,L) in cardiomyocytes from dysferlin-deficient mice and increased frequency of spontaneous sarcoplasmic reticulum Ca2+ release events resulting in pro-arrhythmic contractions. Moreover, cardiomyocytes from dysferlin-deficient mice showed an impaired response to ß-adrenergic receptor stimulation. CONCLUSIONS: Dysferlin is required for TATS biogenesis and maintenance in the heart by controlling the ratio of transversal and axial membrane elements. Absence of dysferlin leads to defects in Ca2+ homeostasis which may contribute to contractile heart dysfunction in dysferlinopathy patients.

CRISPR-Mediated Activation of Endogenous Gene Expression in the Postnatal Heart.

RATIONALE: Genome editing by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 is evolving rapidly. Recently, second-generation CRISPR/Cas9 activation systems based on nuclease inactive dead (d)Cas9 fused to transcriptional transactivation domains were developed for directing specific guide (g)RNAs to regulatory regions of any gene of interest, to enhance transcription. The application of dCas9 to activate cardiomyocyte transcription in targeted genomic loci in vivo has not been demonstrated so far. OBJECTIVE: We aimed to develop a mouse model for cardiomyocyte-specific, CRISPR-mediated transcriptional modulation, and to demonstrate its versatility by targeting Mef2d and Klf15 loci (2 well-characterized genes implicated in cardiac hypertrophy and homeostasis) for enhanced transcription. METHODS AND RESULTS: A mouse model expressing dCas9 with the VPR transcriptional transactivation domains under the control of the Myh (myosin heavy chain) 6 promoter was generated. These mice innocuously expressed dCas9 exclusively in cardiomyocytes. For initial proof-of-concept, we selected Mef2d, which when overexpressed, led to hypertrophy and heart failure, and Klf15, which is lowly expressed in the neonatal heart. The most effective gRNAs were first identified in fibroblast (C3H/10T1/2) and myoblast (C2C12) cell lines. Using an improved triple gRNA expression system (TRISPR [triple gRNA expression construct]), up to 3 different gRNAs were transduced simultaneously to identify optimal conditions for transcriptional activation. For in vivo delivery of the validated gRNA combinations, we employed systemic administration via adeno-associated virus serotype 9. On gRNA delivery targeting Mef2d expression, we recapitulated the anticipated cardiac hypertrophy phenotype. Using gRNA targeting Klf15, we could enhance its transcription significantly, although Klf15 is physiologically silenced at that time point. We further confirmed specific and robust dCas9VPR on-target effects. CONCLUSIONS: The developed mouse model permits enhancement of gene expression by using endogenous regulatory genomic elements. Proof-of-concept in 2 independent genomic loci suggests versatile applications in controlling transcription in cardiomyocytes of the postnatal heart.

KLF15-Wnt-Dependent Cardiac Reprogramming Up-Regulates SHISA3 in the Mammalian Heart.

BACKGROUND: The combination of cardiomyocyte (CM) and vascular cell (VC) fetal reprogramming upon stress culminates in end-stage heart failure (HF) by mechanisms that are not fully understood. Previous studies suggest KLF15 as a key regulator of CM hypertrophy. OBJECTIVES: This study aimed to characterize the impact of KLF15-dependent cardiac transcriptional networks leading to HF progression, amenable to therapeutic intervention in the adult heart. METHODS: Transcriptomic bioinformatics, phenotyping of Klf15 knockout mice, Wnt-signaling-modulated hearts, and pressure overload and myocardial ischemia models were applied. Human KLF15 knockout embryonic stem cells and engineered human myocardium, and human samples were used to validate the relevance of the identified mechanisms. RESULTS: The authors identified a sequential, postnatal transcriptional repression mediated by KLF15 of pathways implicated in pathological tissue remodeling, including distinct Wnt-pathways that control CM fetal reprogramming and VC remodeling. The authors further uncovered a vascular program induced by a cellular crosstalk initiated by CM, characterized by a reduction of KLF15 and a concomitant activation of Wnt-dependent transcriptional signaling. Within this program, a so-far uncharacterized cardiac player, SHISA3, primarily expressed in VCs in fetal hearts and pathological remodeling was identified. Importantly, the KLF15 and Wnt codependent SHISA3 regulation was demonstrated to be conserved in mouse and human models. CONCLUSIONS: The authors unraveled a network interplay defined by KLF15-Wnt dynamics controlling CM and VC homeostasis in the postnatal heart and demonstrated its potential as a cardiac-specific therapeutic target in HF. Within this network, they identified SHISA3 as a novel, evolutionarily conserved VC marker involved in pathological remodeling in HF.

Stabilization of rice bran milling fractions using microwave heating and its effect on storage.

Rice bran tends to become rancid during storage if it is not stabilized. In commercial rice mills, bran is removed in phases using battery of polishers and different fractions of rice bran are produced. The stabilization reduces peroxidase, lipases, lipoxygenase and auto-oxidation enzymatic activities. The bran fractions were stabilized by continuous microwave heating at different treatment combinations (850, 925 and 1000 W; 3, 4.5 and 6 min) and stability of bran fractions were analysed in terms of Free Fatty Acid (FFA), Acid value (AV) and Peroxide value (PV) for 90 days at the interval of 15 days. As power and exposure time increases the FFA, AV and PV are found to be low during storage period. The rancidity level was high in last milling bran fraction and as milling progressed, the rancidity level also increased and it was similar throughout the storage. The bran fractions processed at 925 W to 3 min found to be the suitable condition for stabilization of rice bran milling fractions.

Agonistic and antagonistic roles of fibroblasts and cardiomyocytes on viscoelastic stiffening of engineered human myocardium.

Cardiomyocyte and stroma cell cross-talk is essential for the formation of collagen-based engineered heart muscle, including engineered human myocardium (EHM). Fibroblasts are a main component of the myocardial stroma. We hypothesize that fibroblasts, by compacting the surrounding collagen network, support the self-organization of cardiomyocytes into a functional syncytium. With a focus on early self-organization processes in EHM, we studied the molecular and biophysical adaptations mediated by defined populations of fibroblasts and embryonic stem cell-derived cardiomyocytes in a collagen type I hydrogel. After a short phase of cell-independent collagen gelation (30 min), tissue compaction was progressively mediated by fibroblasts. Fibroblast-mediated tissue stiffening was attenuated in the presence of cardiomyocytes allowing for the assembly of stably contracting, force-generating EHM within 4 weeks. Comparative RNA-sequencing data corroborated that fibroblasts are particularly sensitive to the tissue compaction process, resulting in the fast activation of transcription profiles, supporting heart muscle development and extracellular matrix synthesis. Large amplitude oscillatory shear (LAOS) measurements revealed nonlinear strain stiffening at physiological strain amplitudes (>2%), which was reduced in the presence of cells. The nonlinear stress-strain response could be characterized by a mathematical model. Collectively, our study defines the interplay between fibroblasts and cardiomyocytes during human heart muscle self-organization in vitro and underscores the relevance of fibroblasts in the biological engineering of a cardiomyogenesis-supporting viscoelastic stroma. We anticipate that the established mathematical model will facilitate future attempts to optimize EHM for in vitro (disease modelling) and in vivo applications (heart repair).

Quantum dots as an electron or hole acceptor: on some factors affecting charge transfer in dye-quantum dot composites.

We report a density functional theory (DFT)/time dependent DFT (TDDFT) computational investigation on some factors affecting the nature of charge transfer in CdS quantum dots (QDs) of two different sizes attached to one or two units of dyes among three species viz., coumarine (C343), fluorescein (FLU) and NKX-2388 (NKX). The direction and nature of charge transfers have been ascertained from natural transition orbital analysis. Factors affecting the charge transfer mechanism include the interaction of dyes with QDs, the interaction of a dye with another dye and the effect of solvation. The strength of interaction of the dye and QD depends on the orientation of the dye unit(s) and the type of anchoring group of the dyes and even the direction of charge transfer reverses for different orientation of the dye with respect to the QD in some systems. In addition, hybridized energy levels of the dye-QD composites are formed which leads to direct charge transfer. We observe both direct and indirect charge transfers for different excited states, which is indeed an interesting feature. Interestingly, when two dye molecules are attached to a QD, the direct charge transfer exists between dyes of the same species only. The energy levels, as well as corresponding absorption peaks, exhibit pronounced energy shifts in implicit solvation models.

A context-specific cardiac ß-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart.

Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-ß-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-ß-catenin accumulation mimics the disease situation by triggering TCF7L2 expression. This enhances active chromatin, characterized by increased H3K27ac and TCF7L2 occupancies to cardiac developmental and remodelling genes in vivo. Accordingly, transcriptomic analysis of ß-catenin stabilized hearts shows a strong recapitulation of cardiac developmental processes like cell cycling and cytoskeletal remodelling. Mechanistically, TCF7L2 co-occupies distal genomic regions with cardiac transcription factors NKX2-5 and GATA4 in stabilized-ß-catenin hearts. Validation assays revealed a previously unrecognized function of GATA4 as a cardiac repressor of the TCF7L2/ß-catenin complex in vivo, thereby defining a transcriptional switch controlling disease progression. Conversely, preventing ß-catenin activation post-pressure-overload results in a downregulation of these novel TCF7L2-targets and rescues cardiac function. Thus, we present a novel role for TCF7L2/ß-catenin in CMs-specific chromatin modulation, which could be exploited for manipulating the ubiquitous Wnt pathway.